Organocalcium reagents are highly desirable reagents for organic synthesis. They possess many attributes that are distinct from organomagnesium and other organometallic reagents. For example, they often react stereoselectively and regioselectively. Furthermore, they do not possess the extreme nucleophilicity of such reagents as Grignard reagents. Consequently, organocalcium reagents can generate distinctly different chemistry from that of other organometallic reagents.
The development of organocalcium chemistry has been slow with respect to extensive studies of organometallic reagents of other light metals, such as magnesium. The neglect of organocalcium chemistry has been due, at least in part, to the lack of a facile method of preparing the organocalcium compounds. Furthermore, the few dialkyls and alkyl halides of calcium studied in the early to mid-1900's proved to be thermally unstable, generally insoluble, and difficult to manipulate.
Another impediment to the development of organocalcium chemistry has been the expectation that calcium and organocalcium compounds should parallel that of their magnesium analogs. In fact, calcium is known to more closely resemble sodium rather than magnesium in its chemical reactivity, although calcium is somewhat less reactive than sodium. For example, unlike magnesium but much like sodium, calcium is known to be an excellent reducing agent. Furthermore, unlike magnesium, calcium is soluble in liquid ammonia giving a blue solution similar to the solutions of the Group I metals, which are believed to be solvated metal ions and electrons.
Although there is little known about organocalcium compounds, direct oxidative addition of organic substrates to bulk calcium metal, suspended in a suitable solvent, has traditionally been the method of forming organocalcium compounds. This has been limited, however, by the reduced reactivity of the bulk calcium metal. Although it is not entirely clear, this is presumably due to surface poisoning factors.
Thus, developments in the production of organocalcium compounds have centered around activating the bulk calcium metal. Typically, this has involved alloying of the bulk metal, the addition of activating agents to a reaction mixture, or the use of highly purified bulk metal. For example, Ca amalgam or Ca-Mg alloys have been used to activate the Ca metal to oxidative addition reactions. Iodine has also been used as an activating agent in a reaction mixture.
Although there are several procedures known for the reduction of metal salts to metal powders reactive towards oxidative addition, each metal typically requires unique permutations of the procedures to obtain a reactive species. That is, there is no standardized approach that can produce metal powders of identical, or even similar, reactivity. For example, magnesium metal in the form of a black powder can be obtained by reducing magnesium salts in an ethereal solvent with molten sodium or potassium; however, the use of an alkali metal in conjunction with an electron carrier such as naphthalene can produce magnesium powder of even greater reactivity. These procedures can produce finely divided highly reactive metal powders; however, these procedures are not standardized or generalized.
The organocalcium derivatives RCaX are typically most readily formed when X=I; however, the preparation of RCaX (X=Br, Cl) usually requires activated calcium. Even with activated, or highly pure calcium, few examples of organocalcium halides, or other organocalcium reagents, have actually been prepared. Typically, of the reagents prepared, the overall yields are generally low. Although simple primary and secondary alkyl iodides have been shown to react with highly pure calcium, i.e., Ca containing less than 0.5% Mg and 0.002% Na, in reasonable yields, the tertiary alkyliodocalcium compounds have proven to be very difficult to prepare. In fact, most tertiary alkyls are generally formed in only trace amounts.
Therefore, an object of the invention is to produce a calcium species that is more reactive than those obtained from traditional methods. Another object of the invention is to produce a calcium species that is soluble and highly reactive towards oxidative addition. Yet another object of the invention is the direct production of a wide variety of organocalcium compounds, e.g., aryl and alkyl calcium compounds, particularly tertiary alkyl calcium compounds. Furthermore, an object of the invention is the synthesis of new organic compounds or the synthesis of known organic compounds using more effective and/or more direct synthetic methods.